Based on a human parasite survey of almost 1.5 million people in China, our institute, The Institute of Parasitic Diseases of the Chinese Academy of Preventive Medicine has determined that hookworm infection is a major public health threat to China (particularly in the provinces of the Yangtze River Basin). We estimate that 194 million people are infected with either Ancylostoma duodenale, Necator americanus, or both hookworm species, with up to 50 million cases of hookworm anemia (particularly among women and children). Current control measures that employ specific anthelminthic chemotherapy have been inadequate and unsatisfactory. Therefore we propose to implement modern and innovative biotechnology towards the study and control of human hookworm infection, which has become an important priority for our Ministry of Public Health. Our major focus for control will be molecular vaccine development. In collaboration with the Yale Medical Helminthology Laboratory we will initially examine two recombinant vaccine candidates cloned from A. caninum, directed against either the infective larval and adult blood-feeding stage. These vaccine candidates will be evaluated using our dog model of A. caninum infection, and will be followed by other recombinant polypeptides being developed jointly between our institute and Yale. In association with our Core, we will clone the corresponding molecules from Chinese human hookworm strains, in anticipation of Phase I testing. In order to lay the foundation for this work we will carry out an extensive genetic diversity analysis of the Chinese strains of A. duodenale and N. americanus. To determine the inter- and intra-specific genetic diversity among the two major genera of hookworms, we will employ several molecular techniques, including RAPD analysis and newly developed PCR-RFLP technology. This will allow us to identify regional differences between hookworm species and strains and to identify genetic variation in Chinese strain-specific vaccine candidate molecules.